Faculty Articles
PubMed Identifier
22683694
Rapidly-disintegrating sublingual tablets of epinephrine: role of non-medicinal ingredients in formulation development
Publication Title
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Publication Date
11-1-2012
Keywords
Administration, Sublingual, Anaphylaxis, Cellulose, Chemistry, Pharmaceutical, Drug Compounding, Epinephrine, Excipients, Mannitol, Particle Size, Solubility, Sympathomimetics, Tablets, Time Factors
Abstract
Epinephrine is the drug of choice in the management of anaphylaxis. For first-aid treatment in the community, epinephrine autoinjectors (E-autos) are commonly prescribed, but are underutilized. In our laboratory, we developed a series of first-generation rapidly-disintegrating sublingual tablets (RDSTs) containing 40mg of epinephrine. One RDST had similar bioavailability to epinephrine 0.3mg from an auto-injector, as confirmed in a validated rabbit model, while other formulations containing different non-medicinal ingredients (NMIs) and with similar in vitro characteristics demonstrated much lower bioavailability. Subsequently, we evaluated the effect of changing the grade and proportion of NMIs, specifically mannitol and microcrystalline cellulose (MCC), on the in vitro characteristics of second- and third-generation RDSTs. Weight variation, content uniformity, breaking force, and friability were tested using official USP methods. Novel validated methods that simulate ambient conditions of the sublingual cavity were developed to test disintegration time, wetting time, and dissolution. Using these methods, it was possible to measure the effects of making small changes in NMIs on the in vitro characteristics of the formulations. The RDST formulation that resulted in the best in vitro characteristics contained the optimum proportion of mannitol and a specific ratio of coarse and fine particle grades of MCC. Appropriate comparative testing resulted in the selection of the RDST with the optimum in vitro characteristics.
DOI
10.1016/j.ejpb.2012.05.020
Volume
82
Issue
3
First Page
598
Last Page
604
Disciplines
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
NSUWorks Citation
Rachid, Ousama; Rawas-Qalaji, Mutasem; Simons, F Estelle R; and Simons, Keith J, "Rapidly-disintegrating sublingual tablets of epinephrine: role of non-medicinal ingredients in formulation development" (2012). Faculty Articles. 128.
https://nsuworks.nova.edu/hpd_corx_facarticles/128